Trailing 20-17, Newton marched the Panthers (7-3) on a 13-play, 83-yard drive, capped by a 25-yard scoring pass to Ginn.
The Patriots had one last shot to score, and quarterback Tom Brady led them 62 yards to the Panthers 18-yard line with 3 seconds remaining.
He targeted Rob Gronkowski on the end zone on the final play, but the pass fell short as Gronkowski was being defended by Luke Kuechly.
The Pats wanted an interference call but the officials disagreed, securing the win for Carolina despite a vehement argument from Brady.
Newton completed 19-of-28 passes for 209 yards and three touchdowns while also gaining 62 rushing yards on seven carries as the Panthers recorded a sixth straight win.
Brady went 29-of-40 through the air for 296 yards, a touchdown and an interception for New England (7-3).
Shane Vereen made eight catches for 65 yards.